Hyperlipidemia full review Definition, Classification & All hyperlipidemic drugs mechanism of action

1. Hyperlipidemia
Presented by ;
Mohd siraj
Guided by
Prof . Abdul hadi sultan
prof . Mohd zubair

2. 1. Definitions
2. Classification
3. Mechanism of actions

3. Hyperlipidemia :
Abnormally elevated level of lipid in blood,
these lipids can adhere to the walls of the arteries and
restrict blood flow which creates significant risk of
heart attack and stroke
There are 3 major lipids in our blood
Cholesterol
Triglycerides
Phospholipids

4. Cholestrol : which is necessary for the
synthesis of bile acid.
Triglycerides : which provides energy to
the cell.
Phospholipids : which is the major
component of cell membrane .

5. Lipid produces in liver.
From liver lipids not able to move to
blood stream because they are insoluble in
blood plasma .
So, liver raps protein around the lipid
resulting in new molecule called lipoprotein
Lipoprotein move to blood stream through
out the body

6. Types of lipoprotein :
Very low density lipoprotein
Low density lipoprotein
High density lipoprotein

7. Very low density lipoprotein (VLDL)
It composed of low level of protein , &
high level of cholesterol & triglyceride
Protein
cholesterol
Triglycerides

8. Low density lipoprotein (LDL)
It composed of only protein and cholestrol.
It is also known as bad cholestrol.
Protein
Cholesterol

9. High density lipoprotein (HDL) :
It composed of more amount of protein
and very less amount of cholestrol.
It is also known as good cholestrol
Protein
Cholestrol
Triglyceride

10. Firstly liver releases VLDL in blood
stream
VLDL provides triglyceride to various
cell for function .
After utilizing triglyceride VLDL
becomes LDL which contain only
Protein and cholestrol.
LDL provides cholestrol to various
cell which required .

11. If our body makes too much LDL ,
it will deposited to the walls of artery
causing a fat material called plaque.
Due to which narrow blood vessel
thereby reduce blood flow , that’s
why they are called bad cholestrol.

12. Liver also makes HDL that removes
excess of cholestrol from cells and
plaque , and returns excess cholestrol
to liver that’s why they are called
good cholestrol.

13. classification

14. Drug used to lower lipid levels :
HMG-CoA reductases inhibitors
Fabric acid derivatives
Niacin (nicotinic acid)
Bile acid sequestrates
Cholesterol absorption inhibitors

15. HMG COA REDUCTASE INHIBITOR :
ATORVASTATIN,
FLUVASTATIN,
LOVASTATIN
PRAVATATIN,
ROSUVASTATIN,
FIBRATES :
FENOFIBRATES
GEMFIBROZIL,
CLOFIBRATE
BILE ACID SEQUESTRANTS INHIBITOR :
COLESEVELAM,
COLESTIPOL,
CHOLESTYRAMINE
NICOTINIC ACID :
NIACIN
CHOLESTROL ABSORPTION INHIBITOR :
EZETIMBE

16. Mechanism of action

17. HMG CoA REDUCTASE INHIBITOR :
HMG-CoA
Mevalonic acid
Cholesterol
HMG-CoA
Mevalonic acid
Cholesterol
HMG CoA REDUCTASE
Inhibit the enzyme HMG-CoA reductase , which
Is the rate limiting step in cholesterol synthesis.
In liver cell
HMG CoA REDUCTASE

18. Decrease LDL, Increase HDL , Decrease triglyceride.
The drugs which inhibit HMG CoA reductase
enzyme includes :
Atorvastatin
Fluvastatin
Lovastatin
Pravastatin
Rosavastatin
Side effects : liver toxicity , muscle toxicity.

19. Nicotinic acid
Triglycerides
Fatty acid
Harmone sensative lipase
Fatty acids
Triglyceride VLDL
ADIPOSE
TISSUE
LIVER

20. Normally , Harmone sensative lipase is
responsible for break down of triglyceride
to fatty acids in adipose tissue.
These fatty acids is used by liver to makes
its own triglyceride then become important
component of VLDL

21. Nicotinic acid
Triglycerides
Fatty acid
Harmone sensative lipase
Fatty acids
Triglyceride VLDL
ADIPOSE
TISSUE
LIVER

22. To decrease VLDL production NICOTINIC ACID
Inhibit harmone sensative lipase .
Increase HDL , decrease LDL , decrease triglycerides
The drug which inhibit harmone sensative lipase
is NIACIN .
Side effects : Skin flushing , hyperglycemia,
And hepatotoxicity

23. PPAR α
PPAR α
Fibrate Fibrate
FIBRATES
Fibrates work
primarily by
activating
nuclear
transcription
receptor called
PPAR α
(Peroxisome
proliferator
activated
receptor alpha).

24. PPAR α is found in metabolically active tissues
such as liver and adipose tissue
Binding of fibrates to PPAR α induces
activation or inhibition of certain proteins
involved in lipid metabolism. which
ultimately decrease in the production of
LDL and VLDL .
The drugs belongs to this class include
FINOFIBRATE GEMFIBRIZIL
SIDE EFFECTS : GI distubance ,
rhabdomyolsis have been reported in
patients with impared renal function

25. BILE ACID SEQUESTRANTS :
As we know bile acid are
made from cholestrol .
Liver produce bile acid
and stored in the gall
bladder, and they
excreted into the gut
where they facilitate
digestion & absorption
of lipid
preventing the reabsorption of bile acid

26. This increase in bile acid excretion in turn
creates increase demand for their production
Now bile acid sequestrants basically binds with bile
acid and salt in the small intestine the formation of
this insoluble complex prevents the reabsorption of
of bile acids and thus lead to their excretion
BILE ACID SEQUESTRANT + BILE ACID = FORMS A COMPLEX

27. Since bile acid are made from cholesterol
liver cell increase their number of LDL
receptors to bring in more LDL
cholestrol in order to meet this new
demand so the end result is decreased
levels of circulating LDL
The drugs belongs to this class
include
CLESEVELAM,
COLESTIPOL ,
CHOLESTYRAMINE
SIDE EFFECTS : constipation
nausea are the common side
effects

28. CHOLESTEROL ABSORPTION
INHIBITORS
Under normal condition
Mechanism of cholesterol absorption in small
intestine
Free cholesterol that comes either from bile or
dietary sources first binds to protein abbreviated
NPC1L1 which is located in the plasma membrane
of the cells known as enterocytes that lines the
intestinal walls .

30. Upon endocytosis the cholesterol is released
and the NPC1L1 return back to the plasma
membrane
This Binding then triggers endocytosis
which utilizes protein complex called
clathrin AP2 that works on the cell
membrane to internalize the cholesterol
cargo upon

32. Now the cholesterol absorption inhibitors
simply binds to NPC1L1 and inhibits its ability
to intract with clathrin AP2 complex that is
necessary for endocytosis this lead to
decreased dilevery of intestinal cholesterol to
the liver
Which in turn causes decrease in hepatic
cholesterol level & ultimately increased
clearance of LDL cholesterol from the
circulation

33. EZETIMBE

34. The side effects of ezetimibe are mild
and few which makes it a good choice for
patients with intolarant or unresponsive to
statins .
Currently the only drug belongs to this
class is EZETIMBE

35. THANK YOU